Background and Purpose:: The purpose of this study was to investigate changes in brain current-source density (CSD) of the high frequency band (22–30 Hz) induced by zonisamide (ZNS) in patients with newly diagnosed epilepsy and to correlate with the cognitive performances. Methods:: We conducted a 24-week, open-labeled, prospective study in 19 patients. Eelectroencephalography (EEG) and neuropsychological tests (NPs) were conducted at baseline and 24 weeks after starting the medication. Six patients were excluded due to artifacts in EEG. One patient did not attend follow-up studies. Twelve patients who completed follow-up EEG and NPs were included. We used low-resolution brain electromagnetic tomography to determine CSD, and we obtained statistical nonparametric maps for the high beta frequency band (22–30 Hz) between pretreatment EEGs and post-treatment EEGs. Results:: The CSD in the 22–30 Hz band decreased in the superior frontal, middle frontal, anterior cingulate, precentral, postcentral, and inferior parietal gyri of the left hemisphere, and the middle frontal, inferior frontal and anterior cingulate gyri of the right hemisphere. Among the NPs items, the performance of verbal fluency was significantly impaired after the 24-week ZNS trial. Conclusions:: The CSD changes suggest ZNS may diminish the activity of cerebral networks related to verbal fluency.